Chronic itch is an often difficult and sometimes debilitating symptom of many skin diseases and other disorders. Researchers have been trying to determine for decades if there are separate neuronal pathways for pain and itch. However, studies of underlying mechanisms have long been complicated and hindered by the difficulties of distinguishing itch from pain at molecular and cellular levels. Now, researchers supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered itch-specific neurons which express a protein known as gastrin-releasing peptide receptor (GRPR) in the spinal cord of mice. Without GRPR-expressing neurons, there is no sensation of itch. The present study, recently published in Science, provides the most comprehensive behavioral evidence to support the idea that distinct subsets of neurons transmit the different sensations of pain and itch in the spinal cord.
Zhou-Feng Chen, Ph.D., of Washington University School of Medicine Pain Center in St. Louis, Mo., and his colleagues had suspected from their previous work that GRPR might be an itch-specific protein in the spinal cord, and that neurons containing it transmitted signals which are perceived as itch. Dr. Chen and his colleagues designed an experiment to test whether removing GRPR-expressing neurons could alleviate itch, but preserve the pain response. The researchers injected mice with a toxin (bombesin-sap) designed to bind to a group of neurons expressing GRPR. Once the toxin entered the neuron, the neuron died, normally within two weeks of injection. To confirm bombesin-sap was destroying only the neurons containing GRPR, the scientists analyzed subpopulations of neurons in the spinal cord by using lamina-specific molecular markers and found that subpopulations of neurons expressing other neuronal markers were not affected by the toxin. Then, researchers observed as the mice were treated with stimuli which normally would induce itch and cause them to scratch. The mice whose neurons had been destroyed by the toxin did not exhibit scratching behavior. However, the death of the neurons did not appear to interfere with the mice's ability to feel and react to pain.
This study helps illuminate a previously elusive mechanism by which an itch-specific sensation travels through the spinal cord to be perceived as itch by the brain. Such a discovery should pave the way for future studies of mechanisms that regulate the development of chronic itch, and make it possible, for the first time, to design better treatments to control intractable itch.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.
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Sun Y, Zhao Z, Meng X, Yin J, Liu X, and Chen Z. Cellular Basis of Itch Sensation. Science. 2009 Sept 18;325:1531-4.